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Table 2 Summary of protein biomarkers related to various pathophysiological processes that are associated with cardiovascular disease (CVD)

From: Sudden Cardiac Death (SCD) – risk stratification and prediction with molecular biomarkers

Process Biomarkers Association with CVD Strength of evidencea Ref
Oxidative stress Reduced (cysteine and glutathione) and oxidized (cystine and glutathione disulphide) aminothiols High cystine (oxidized) and low glutathione (reduced) levels were associated with higher mortality in patients with CAD ++ [45]
Heat shock protein 70 (HSP70) High levels of HSP70 were associated with low CAD risk + [47]
High HSP70 levels were associated with increased risk of cardiac death   [48]
Inflammation Interleukin (IL) such as IL-6 and IL-18 Higher IL-6 levels were associated with SCD and was an independent predictor of sudden death +++ [51]
High levels of IL-6 were associated with increased burden of atherosclerosis and higher risk of major adverse cardiac events (MACE) risk   [52]
Higher IL-6 levels were associated with atherosclerotic cardiovascular disease (ASCVD) events, heart failure (HF) and mortality   [53]
[55]
Higher levels of IL-18 and IL-12 were associated with increased risk of cardiovascular events   
C-reactive protein (CRP) High CRP levels were associated with greater mortality and risk of cardiovascular disease ++ [60]
CRP levels were not significantly associated with sudden death and SCD risk   [51, 61]
Lipoprotein-associated phospholipase A2 (Lp-PLA2) Higher Lp-PLA2 levels were associated with increased risk of coronary heart disease and was an independent predictor of CHD events + [63, 64]
Myeloperoxidase (MPO) MPO levels were associated with the incidence and severity of CAD + [66]
Urokinase-type plasminogen activator receptor (uPAR) High suPAR levels were associated with increased risk of CVD ++ [68, 69]
Matrix metalloproteinases (MMP) Higher levels of MMP-1, − 2, − 8 and − 9 were associated with acute coronary syndromes and CAD + [74, 75]
Pentraxin-3 (PTX3) PTX3 was associated with higher risk of mortality in patients with chronic heart failure + [72]
Neurohormonal regulation Renin and aldosterone Higher plasma renin and aldosterone levels were associated with increased risk of cardiovascular mortality and adverse outcome in ST-elevation myocardial infarction (STEMI) +++ [77,78,79]
Adrenomedullin (ADM) High ADM levels were associated with heart failure ++ [81, 82]
Mid-regional pro–atrial natriuretic peptide (MR-proANP) demonstrated diagnostic and prognostic utility in patients with acute heart failure (AHF)   [80, 84]
Copeptin High copeptin levels were associated with increased mortality, readmissions, and emergency department visits in patients with acute heart failure as well as excess mortality in patients with chronic HF + [86, 87]
Hemodynamic properties Natriuretic peptides (NP), i.e. (B-type natriuretic peptide) BNP or (N-terminal pro B-type natriuretic peptide) NT-proBNP Higher NT-proBNP levels were associated with increased risk of SCD +++ [61, 89]
High BNP levels were an independent predictor of sudden death in patient with chronic heart failure   [90]
High BNP levels were associated with higher risk of death/mortality in patients with acute myocardial infarction   [91]
Myocardial stress, necrosis, fibrosis and tissue regeneration Cardiac troponins (cTn) High levels of cTn were associated with the risk of death from cardiovascular causes, myocardial infarction, stroke or heart failure +++ [92,93,94,95,96]
High levels of cTn were associated with the severity and progression of chronic heart failure   [97]
Osteopontin High osteopontin levels were associated with left ventricular dysfunction and reduced levels were correlated with good response to heart failure therapies + [98]
ST2 receptor High ST2 levels were associated with cardiovascular mortality in chronic heart failure patients + [99]
Growth differentiator 15 (GDF-15) High GDF-15 levels were associated with risk of developing CVD and mortality + [100]
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